tbuckley/cabot-search huggingface dataset:
Selective STING stimulation in dendritic cells primes antitumor T cell responses
Authors: Bakhos Jneid, Aurore Bochnakian, Caroline Hoffmann, Fabien Delisle, Emeline Djacoto, Philémon Sirven, Jordan Denizeau, Christine Sedlik, Yohan Gerber-Ferder, Frédéric Fiore, Ramazan Akyol, Carine Brousse, Robert Kramer, Ian Walters, Sylvain Carlioz, Hélène Salmon, Bernard Malissen, Marc Dalod, Eliane Piaggio, Nicolas Manel
Journal: Science Immunology (2023)

T cells that recognize tumor antigens are crucial for mounting antitumor immune responses. Induction of antitumor T cells in immunogenic tumors depends on STING, the intracellular innate immune receptor for cyclic guanosine monophosphate–adenosine monophosphate (cGAMP) and related cyclic dinucleotides (CDNs). However, the optimal way to leverage STING activation in nonimmunogenic tumors is still unclear. Here, we show that cGAMP delivery by intratumoral injection of virus-like particles (cGAMP-VLP) led to differentiation of circulating tumor-specific T cells, decreased tumor regulatory T cells (T regs ), and antitumoral responses that synergized with PD1 blockade. By contrast, intratumoral injection of the synthetic CDN ADU-S100 led to tumor necrosis and systemic T cell activation but simultaneously depleted immune cells from injected tumors and induced minimal priming of circulating tumor-specific T cells. The antitumor effects of cGAMP-VLP required type 1 conventional dendritic cells (cDC1), whereas ADU-S100 eliminated cDC1 from injected tumors. cGAMP-VLP preferentially targeted STING in dendritic cells at a 1000-fold smaller dose than ADU-S100. Subcutaneous administration of cGAMP-VLP showed synergy when combined with PD1 blockade or a tumor T reg -depleting antibody to elicit systemic tumor-specific T cells and antitumor activity, leading to complete and durable tumor eradication in the case of tumor T reg depletion. These findings show that cell targeting of STING stimulation shapes the antitumor T cell response and identify a therapeutic strategy to enhance T cell–targeted immunotherapy.
Anti–PD-1 antibodies recognizing the membrane-proximal region are PD-1 agonists that can down-regulate inflammatory diseases
Authors: Kensuke Suzuki, Masaki Tajima, Yosuke Tokumaru, Yuya Oshiro, Satoshi Nagata, Haruhiko Kamada, Miho Kihara, Kohei Nakano, Tasuku Honjo, Akio Ohta
Journal: Science Immunology (2023)

The PD-1 receptor triggers a negative immunoregulatory mechanism that prevents overactivation of immune cells and subsequent inflammatory diseases. Because of its biological significance, PD-1 has been a drug target for modulating immune responses. Immunoenhancing anti–PD-1 blocking antibodies have become a widely used cancer treatment; however, little is known about the required characteristics for anti–PD-1 antibodies to be capable of stimulating immunosuppressive activity. Here, we show that PD-1 agonists exist in the group of anti–PD-1 antibodies recognizing the membrane-proximal extracellular region in sharp contrast to the binding of the membrane-distal region by blocking antibodies. This trend was consistent in an analysis of 81 anti-human PD-1 monoclonal antibodies. Because PD-1 agonist antibodies trigger immunosuppressive signaling by cross-linking PD-1 molecules, Fc engineering to enhance FcγRIIB binding of PD-1 agonist antibodies notably improved human T cell inhibition. A PD-1 agonist antibody suppressed inflammation in murine disease models, indicating its clinical potential for treatment of various inflammatory disorders, including autoimmune diseases.
Electrically stimulated 3D bioprinting of gelatin-polypyrrole hydrogel with dynamic semi-IPN network induces osteogenesis via collective signaling and immunopolarization
Authors: Sayan Deb Dutta, Keya Ganguly, Aayushi Randhawa, Tejal V. Patil, Dinesh K. Patel, Ki-Taek Lim
Journal: Biomaterials (2023)
The pre-Descemet's layer (Dua's layer, also known as the Dua-Fine layer and the pre-posterior limiting lamina layer): Discovery, characterisation, clinical and surgical applications, and the controversy
Authors: Harminder S. Dua, Rui Freitas, Imran Mohammed, Darren S.J. Ting, Dalia G. Said
Journal: Progress in Retinal and Eye Research (2023)

The pre-Descemet's layer/Dua's layer, also termed the Dua-Fine layer and the pre-posterior limiting lamina layer, lies anterior to the Descemet's membrane in the cornea, is 10 μm (range 6–16) thick, made predominantly of type I and some type VI collagen with abundant elastin, more than any other layer of the cornea. It has high tensile strength (bursting pressure up to 700 mm of Hg), is impervious to air and almost acellular. At the periphery it demonstrates fenestrations and ramifies to become the core of the trabecular meshwork, with implications for intraocular pressure and glaucoma. It has been demonstrated in some species of animals. The layer has assumed considerable importance in anterior and posterior lamellar corneal transplant surgery by improving our understanding of the behaviour of corneal tissue during these procedures, improved techniques and made the surgery safer with better outcomes. It has led to the innovation of new surgical procedures namely, pre-Descemet's endothelial keratoplasty, suture management of acute hydrops, DALK-triple and Fogla's mini DALK. The discovery and knowledge of the layer has introduced paradigm shifts in our age old concepts of Descemet's membrane detachment, acute corneal hydrops in keratoconus and Descemetoceles, with impact on management approaches. It has been shown to contribute to the pathology and clinical signs observed in corneal infections and some corneal dystrophies. Early evidence suggests that it may have a role in the pathogenesis of keratoconus in relation to its elastin content. Its contribution to corneal biomechanics and glaucoma are subjects of current investigations.
T follicular helper cells in cancer
Authors: Nicolás Gutiérrez-Melo, Dirk Baumjohann
Journal: Trends in cancer (2023)

T follicular helper (Tfh) cells provide essential help to B cells for effective antibody-mediated immune responses. Although the crucial function of these CD4+ T cells in infection and vaccination is well established, their involvement in cancer is only beginning to emerge. Increased numbers of Tfh cells in Tfh cell-derived or B cell-associated malignancies are often associated with an unfavorable outcome, whereas in various solid organ tumor types of non-lymphocytic origin, their presence frequently coincides with a better prognosis. We discuss recent advances in understanding how Tfh cell crosstalk with B cells and CD8+ T cells in secondary and tertiary lymphoid structures (TLS) enhances antitumor immunity, but may also exacerbate immune-related adverse events (irAEs) such as autoimmunity during immune checkpoint blockade (ICB) and cancer immunotherapy.
Obturator Nerve Injury in Robotic Pelvic Surgery: Scenarios and Management Strategies
Authors: Anibal La Riva, Aref S. Sayegh, Laura C. Perez, Jaime Poncel, Luis G. Medina, Brittany Adamic, Ryan Powers, Giovanni E. Cacciamani, Monish Aron, Inderbir Gill, Rene Sotelo
Journal: European Urology (2023)
ROS‐Responsive Blended Nanoparticles: Cascade‐Amplifying Synergistic Effects of Sonochemotherapy with On‐demand Boosted Drug Release During SDT Process
Authors: Pengying Wu, Wei Dong, Xuyan Guo, Xiaoyang Qiao, Shifang Guo, Lei Zhang, Mingxi Wan, Yujin Zong
Journal: Advanced Healthcare Materials (2023)

The original version of this article contained previously unnoticed mistakes in Figure 5D (Free IR780 and IR780/PTL-NPs+US3+NAC groups), and, in the article's Supplementary Information, inadvertent clerical mistakes in Figure S1 (synthesis route of PTX-TL: DCC reagent was forgotten to add, synthesis route of PTX-TL-PEG 1K -NH 2 : DMAP and DMF reagents were wrongly written as HOBT and CH 2 CI 2 , respectively) and Figure S7 ("Heart" row: IR780/PTL-NPs+US3 group, "Lung" row: PTL-NPs+US3 and IR780/PTL-NPs groups, "Kidney" row: IR780/PTL-NPs+US3 group.The corrected images are now incorporated below according to the raw data (Figure 5D and Figure S7) and the correct description (Figure S1).These corrections do not affect or change the results and conclusion of this work.Figure 5D.Representative images of Calcein AM/PI double staining showing live/dead cells.
Mussel‐Inspired Tough Hydrogel with In Situ Nanohydroxyapatite Mineralization for Osteochondral Defect Repair
Authors: Donglin Gan, Zhixiong Wang, Chaoming Xie, Xiao Wang, Wensi Xing, Xiang Ge, Huipin Yuan, Kefeng Wang, Hui Tan, Xiong Lu
Journal: Advanced Healthcare Materials (2023)

Adv. Healthcare Mater. 2019, 8, 1901103 https://doi.org/10.1002/adhm.201901103 In the original version of this article, Figure 8d was accidentally a duplicate of Figure 8c. The corrected Figure with the correct Figure 8d is shown below. These changes do not affect the overall results and conclusions from this work.
Biomimicking Leaf‐Vein Engraved Soft and Elastic Membrane Promotes Vascular Reconstruction (Adv. Healthcare Mater. 2/2023)
Authors: Jinghan Fang, Huaqian Liu, Wei Qiao, Tianpeng Xu, Yuhe Yang, Huizhi Xie, Chun‐Hei Lam, Kelvin W. K. Yeung, Xin Zhao
Journal: Advanced Healthcare Materials (2023)

Leaf Veins The leaf vein is the “vascular system” in plants. In article 2201220 by Kelvin W. K. Yeung, Xin Zhao, and co-workers, a leaf-vein micropattern is engraved on a PGLADMA polymer membrane, serving as “running tracks” for vascular endothelial cells to facilitate hierarchical and functional vascular reconstruction. The leaf-vein engraved membrane can induce vascular endothelial cell differentiation, vasculature reconstruction, and vessel maturation.
Enhanced Tumor Accumulation of Multimodal Magneto‐Plasmonic Nanoparticles via an Implanted Micromagnet‐Assisted Delivery Strategy (Adv. Healthcare Mater. 2/2023)
Authors: Sajanlal R. Panikkanvalappil, Sharath K. Bhagavatula, Kyle Deans, Oliver Jonas, Mohammad Rashidian, Shruti Mishra
Journal: Advanced Healthcare Materials (2023)

Microtopography In article 2201585, Sajanlal R. Panikkanvalappil and co-workers demonstrate an efficient tumor targeting strategy to deliver systemically administered nanoparticles (NPs) into solid tumors. This technique involves intratumoral implantation of micromagnets, which facilitate enhanced tumor accumulation of the novel multimodal magneto-plasmonic NPs at a micromagnet-implanted tumor compared to the control tumor. These magneto-plasmonic NPs show unique therapeutic, sensing, and imaging capabilities.
PerfU-Net: Baseline infarct estimation from CT perfusion source data for acute ischemic stroke
Authors: Lucas de Vries, Bart J. Emmer, Charles B.L.M. Majoie, Henk A. Marquering, Efstratios Gavves
Journal: Medical Image Analysis (2023)

CT perfusion imaging is commonly used for infarct core quantification in acute ischemic stroke patients. The outcomes and perfusion maps of CT perfusion software, however, show many discrepancies between vendors. We aim to perform infarct core segmentation directly from CT perfusion source data using machine learning, excluding the need to use the perfusion maps from standard CT perfusion software. To this end, we present a symmetry-aware spatio-temporal segmentation model that encodes the micro-perfusion dynamics in the brain, while decoding a static segmentation map for infarct core assessment. Our proposed spatio-temporal PerfU-Net employs an attention module on the skip-connections to match the dimensions of the encoder and decoder. We train and evaluate the method on 94 and 62 scans, respectively, using the Ischemic Stroke Lesion Segmentation (ISLES) 2018 challenge data. We achieve state-of-the-art results compared to methods that only use CT perfusion source imaging with a Dice score of 0.46. We are almost on par with methods that use perfusion maps from third party software, whilst it is known that there is a large variation in these perfusion maps from various vendors. Moreover, we achieve improved performance compared to simple perfusion map analysis, which is used in clinical practice.
Mimicker of Osteoblastic Skeletal Metastasis on 18F-FDG PET/CT Scan in a Case of Primary Mediastinal Germ Cell Tumor
Authors: Rachita Rungta, Melvika Pereira, Divya Shivdasani, Debdip Roy, Shreya Dang, Himanshu Jaiswal, Aishwarya Wagle, Natasha Singh
Journal: Clinical Nuclear Medicine (2023)

Abstract Primary mediastinal germ cell tumors are uncommon tumors, of which the nonseminomatous type is more likely to metastasize than the seminomatous type. Primary mediastinal germ cell tumors may also present with superior vena cava obstruction. Here, we present this case of primary mediastinal germ cell tumor with superior vena cava obstruction causing dilatation of collaterals in dorsal intravertebral venous plexus, which strongly mimics sclerotic skeletal lesions/metastasis on a Contrast-enhanced CT scan and also appears FDG avid on PET scan. Herein, we can differentiate the two by just a simple review of plain CT scan image.
PET/CT Reveals Localized Inflammation in the Temporal, Vertebral, and Lower Extremity Arteries in Giant Cell Arteritis
Authors: Nozomi Kawamata, Yoshiyuki Abe, Ayako Makiyama, Karin Ashizawa, Naoto Tamura
Journal: Clinical Nuclear Medicine (2023)

Abstract 18 F-FDG PET/CT is increasingly being used in the diagnosis of systemic vasculitis syndromes, especially large-vessel vasculitis. We present a case of giant cell arteritis in an 84-year-old man who exhibited large-vessel lesions in the periphery but none in the trunk. This case highlights the usefulness of PET/CT for revealing localized inflammation.
Culturally safe, appropriate, and high-quality breast cancer screening for transgender people: A scoping review
Authors: Imogen Ramsey, Kate Kennedy, Greg Sharplin, Marion Eckert, Micah D. J. Peters
Journal: International Journal of Transgender Health (2023)

Background There is a recognized need for evidence to inform breast cancer screening guidelines and services for transgender people, who face barriers to accessing appropriate and inclusive health care.Aims This review summarized evidence for breast cancer risk and screening guidelines in transgender individuals, including the potential impact of gender-affirming hormone therapy (GAHT); factors that may influence screening decision-making and behaviors; and considerations for providing culturally safe, high-quality screening services.Methods A protocol was developed based on the Joanna Briggs Institute scoping review methodology. Searches were performed in Medline, Emcare, Embase, Scopus, and the Cochrane Library for articles reporting information on the provision of culturally safe, high-quality breast cancer screening services for transgender people.Results We identified 57 sources for inclusion: 13 cross-sectional studies, 6 case reports, 2 case series, 28 review or opinion articles, 6 systematic reviews, 1 qualitative study, and 1 book chapter. Evidence on rates of breast cancer screening among transgender people and the association between GAHT and breast cancer risk was inconclusive. Factors negatively associated with cancer screening behaviors included socioeconomic barriers, stigma, and lack of health provider awareness of transgender health issues. Breast cancer screening recommendations varied and were generally based on expert opinion due to the lack of clear evidence. Considerations for providing culturally safe care to transgender people were identified and mapped to the areas of workplace policies and procedures, patient information, clinic environment, professional conduct, communication, and knowledge and competency.Discussion Screening recommendations for transgender individuals are complicated by the lack of robust epidemiological data and clear understanding of the role GAHT may play in breast cancer pathogenesis. Guidelines have been developed based on expert opinion and are subsequently not uniform or evidence based. Further work is required to clarify and consolidate recommendations.
Treatable traits in interstitial lung diseases: a call to action
Authors: Francesco Amati, Paolo Spagnolo, Justin M Oldham, Christopher J Ryerson, Anna Stainer, Andrea Gramegna, Marco Mantero, Donato Lacedonia, Nicola Sverzellati, Luca Richeldi, Francesco Blasi, Stefano Aliberti
Journal: The Lancet Respiratory Medicine (2023)
Evaluating post-treatment Loa loa microfilarial densities to classify serious adverse events caused by ivermectin: a retrospective analysis
Authors: Charlotte Boullé, Cédric B Chesnais, Joseph Kamgno, Jacques Gardon, Jean-Philippe Chippaux, Stéphane Ranque, André Garcia, Sébastien D Pion, Michel Boussinesq
Journal: The Lancet Microbe (2023)

The elimination of onchocerciasis requires increasing ivermectin treatment coverage in communities hypoendemic for onchocerciasis. In areas where loiasis is co-endemic, this approach is complicated by the risk of serious adverse events following treatment with ivermectin in individuals with a high Loa loa microfilarial density (MFD). We aimed to evaluate the extent to which the pre-treatment MFD can be inferred from post-treatment MFDs.For this retrospective analysis, we used data from seven clinical or community trials (six were used for the main analysis and one for the secondary analysis) conducted in Cameroon, in which MFDs were measured both before and after (within 14 days) receiving a single dose of ivermectin (150-200 μg/kg bodyweight). The primary objective was to establish the receiver operating characteristic curves and the corresponding area under the curve statistics of MFD measured after treatment to classify pre-treatment MFD (MFDD0) according to common risk thresholds of serious adverse events. We assessed the performance of post-treatment MFD to accurately classify MFDD0 according to commonly used thresholds using bootstrap procedures.281 individuals with MFD measurements available before and 3-10 days after ivermectin treatment were enrolled. Our results show that an MFD of more than 3500 L loa microfilariae per mL of blood (mf per mL) 3 or 4 days after treatment indicates a 68·6% chance (positive predictive value) of an MFDD0 of more than 20 000 mf per mL. An MFD of more than 3500 mf per mL at day 5-10 corresponds to a 72·2% chance of having an MFDD0 of more than 20 000 mf per mL. Conversely, an MFD of less than 2500 microfilariae per mL at day 3-4 or day 5-10 corresponds to a probability of 92·3% or 92·8% (negative predictive value) of having MFDD0 of less than 20 000 mf per mL. An MFD less than 1500 mf per mL on days 3-4 after treatment was associated with a 78·3% probability of having an MFDD0 less than 8000 mf per mL; this probability increased to 89·6% on days 5-10 after treatment.The MFD threshold of 1000 mf per mL within 1 month of treatment, which is commonly used to attribute the occurrence of a serious adverse event to ivermectin, should be revised. In this study, we present tables that can help to assess this attributability as part of mass or individual treatments.None.
Probiotic for pathogen-specific Staphylococcus aureus decolonisation in Thailand: a phase 2, double-blind, randomised, placebo-controlled trial
Authors: Pipat Piewngam, Sunisa Khongthong, Natthrit Roekngam, Yongyuth Theapparat, Somkiat Sunpaweravong, Damrongsak Faroongsarng, Michael Otto
Journal: The Lancet Microbe (2023)
Targeting Pulmonary Hypertension Caused by Pulmonary Fibrosis: A Promising Natural Killer T Cell–based Therapy
Authors: Zi-Hao Wang, Qiong Zhou
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Targeting Pulmonary Hypertension Caused by Pulmonary Fibrosis: A Promising NKT Cell-based Therapy." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp. –
Patients with Asian-type DEL can safely be transfused using RhD-positive blood
Authors: Yanli Ji, Yalin Luo, Jizhi Wen, Yuanfan Sun, Shuangshuang Jia, Chunquan Ou, Wenbing Yang, Jingwang Chen, Hanshen Ye, Xiangfu Liu, Yongneng Liang, Zhigang Lu, Ying Feng, Xinzhong Wu, Muzhou Xiao, Jiankun Mo, Zhenhai Zhou, Zhen Wang, Zhijian Liao, Junhu Chen, Ling Wei, Guangping Luo, Sentot Santoso, Yann Fichou, Willy A Flegel, Chaopeng Shao, Chengyao Li, Rui Zhang, Yongshui Fu
Journal: Blood (2023)

Red blood cells (RBCs) of Asian-type DEL phenotype express few RhD proteins and are typed as serologic RhD-negative (D-) phenotype in routine testing. RhD-positive (D+) RBC transfusion for patients with Asian-type DEL has been proposed but has not been generally adopted because of a lack of direct evidence regarding its safety and the underlying mechanism. We performed a single-arm multicenter clinical trial to document the outcome of D+ RBC transfusion in patients with Asian-type DEL; none of the recipients (0/42; 95% confidence interval, 0-8.40) developed alloanti-D after a median follow-up of 226 days. We conducted a large retrospective study to detect alloanti-D immunization in 4045 serologic D- pregnant women throughout China; alloanti-D was found only in individuals with true D- (2.63%, 79/3009), but not in those with Asian-type DEL (0/1032). We further retrospectively examined 127 serologic D- pregnant women who had developed alloanti-D and found none with Asian-type DEL (0/127). Finally, we analyzed RHD transcripts from Asian-type DEL erythroblasts and examined antigen epitopes expressed by various RHD transcripts in vitro, finding a low abundance of full-length RHD transcripts (0.18% of the total) expressing RhD antigens carrying the entire repertoire of epitopes, which could explain the immune tolerance against D+ RBCs. Our results provide multiple lines of evidence that individuals with Asian-type DEL cannot produce alloanti-D when exposed to D+ RBCs after transfusion or pregnancy. Therefore, we recommend considering D+ RBC transfusion and discontinuing anti-D prophylaxis in patients with Asian-type DEL, including pregnant women. This clinical trial is registered at www.clinicaltrials.gov as #NCT03727230.
Faster lung function decline in people living with HIV despite adequate treatment: a longitudinal matched cohort study
Authors: Rebekka Faber Thudium, Andreas Ronit, Shoaib Afzal, Yunus Çolak, Julie Lyng Forman, Fernando Mendo, Fabian Chen, Vicente Estrada, Nagalingeswaran Kumarasamy, Børge G Nordestgaard, Jens Lundgren, Jørgen Vestbo, Ken M Kunisaki, Susanne Dam Nielsen
Journal: Thorax (2023)

Introduction Chronic lung disease is common among people living with HIV (PLWH). We hypothesised that PLWH receiving antiretroviral therapy (ART) have faster lung function decline than matched controls. Methods We performed a prospective matched cohort study by including ART-treated PLWH from the Copenhagen Co-morbidity in HIV Infection Study (n=705) and the INSIGHT Strategic Timing of Antiretroviral Treatment Pulmonary Substudy (n=425) and frequency matched population controls from the Copenhagen General Population Study (n=2895) in a 1:3 ratio. Eligible participants were ≥25 years old and had two spirometry tests separated by at least 2 years of follow-up. Forced expiratory volume in 1 s (FEV 1 ) decline (mL/year) was compared between PLWH and controls using a linear mixed model adjusted for age, sex, ethnicity and smoking status. Effect modification by smoking was investigated in subgroup analyses. Results The majority of PLWH were virally suppressed (96.1%). The adjusted mean annual decline in FEV 1 was faster in PLWH than in controls with 36.4 (95% CI 33.7 to 39.1) vs 27.9 (95% CI 26.9 to 28.8) mL/year, yielding a difference of 8.5 (95% CI 5.6 to 11.4) mL/year. The association between HIV and FEV 1 decline was modified by smoking, with the largest difference in current smokers (difference: 16.8 (95% CI 10.5 to 23.0) mL/year) and the smallest difference in never-smokers (difference: 5.0 (95% CI 0.7 to 9.3) mL/year). FEV 1 decline &gt;40 mL/year was more prevalent in PLWH (adjusted OR: 1.98 (95% CI 1.67 to 2.34)). Conclusion Well-treated PLWH have faster lung function decline than controls and smoking seems to modify this association, suggesting that smoking may lead to more rapid lung function decline in PLWH than in controls.